Structure of the rat p53 tumor suppressor gene

• Published in: Nucleic acids research Vol. 21; no. 3; pp. 713 - 717
• Main Authors: Hulla, Janis E., Schneider, Richard P.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 11.02.1993
• Subjects: Animals; Base Sequence; Biological and medical sciences; Blotting, Southern; Cloning, Molecular; DNA, Neoplasm; Fundamental and applied biological sciences. Psychology; Genes, p53; Genes. Genome; Humans; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Polymerase Chain Reaction; Rats; RNA Splicing; Vertebrata; Mammalia; Exon; Intron; Rat; Rodentia; Gene organization; Polymorphism; Tumor suppressor gene
• ISSN: 0305-1048; 1362-4954; 1362-4962; 1362-4962
• DOI: 10.1093/nar/21.3.713

Aberration within the p53 tumor suppressor gene is the most frequently identified genetic damage in human cancer. Regulatory functions proposed for the p53 protein include modulation of the cell cycle, cellular differentiation, signal transduction, and gene expression. Additionally, the p53 gene product may guard the genome against incorporation of damaged DNA. To facilitate study of its role in carcinogenesis using a common animal model, we determined the structure of the rat p53 gene. We identified 18 splice sites and defined 25 bases of the intervening sequences adjacent to these sites. We also discovered an alielic polymorphism that occurs within intron 5 of the gene. The rat gene approximates the mouse ortholog. It is 12 kb in length with thenon-coding exon 1 separated from exon 2 by 6.2 kb of intervening sequence. The location and size of au rat gene introns approximate those of the mouse. Whereas the mouse and human genes each contain 11 exons, the rat p53 gene is composed of only 10. No intervening sequence occurs between the region of the rat gene corresponding to exons 6 and 7 of the mouse and human p53 genes. This implies intron 6 may be functionally insignificant for species in which it is retained. To extrapolate to p53 involvement in human tumorigenesis, we suggest that mutational events within intron 6 may not be of pathological significance unless splicing is hindered.